The proposed research plan is designed to study the in vitro interrelationship of human natural killer (NK) cells, interferon(s), and fresh neoplastic cells from patients with leukemia/lymphoma. Our immediate objectives are to further characterize the NK susceptibility, as mediated by both resting and interferon-activated NK cells, of purified subpopulations of fresh tumor targets from patients with acute and chronic leukemia, as well as from patients with non-Hodgkin lymphomas, and to better characterize the presence or absence of effector NK cells from these same tumor-bearing patients by methods which enrich for human NK cells. Further goals are to test the hypothesis that there is killing of NK susceptible fresh tumor targets as mediated by autologous NK cells, and to further show that this autologous interaction is enhanced by interferon and interferon inducers in vitro. Another extremely important aspect of the proposed project is to test the hypothesis that interferon, itself, does not induce an in vitro state of refractoriness to allogeneic and/or autologous NK lysis of previously susceptible fresh leukemia/lymphoma targets (ie, interferon protection of neoplastic targets). An important corollary is to further test the hypothesis using in vitro techniques, that normal, nonneoplastic counterparts are protected from NK lysis with interferon, and to further understand, if both neoplastic and nonneoplastc targets are interferon protected in vitro, how to dissociate the two targets such that the nonneoplastic cells are protected and neoplastic cells are lysed. Our ultimate goal is to relate the above findings to the potential feasibility of interferon and interferon inducers as an immunotherapeutic treatment modality for patients with NK susceptible human leukemias and related lymphomas.